Environmental risk factors of type 2 diabetes-an exposome approach

Type 2 diabetes is one of the major chronic diseases accounting for a substantial proportion of disease burden in Western countries. The majority of the burden of type 2 diabetes is attributed to environmental risks and modifiable risk factors such as lifestyle. The environment we live in, and changes to it, can thus contribute substantially to the prevention of type 2 diabetes at a population level. The ‘exposome’ represents the (measurable) totality of environmental, i.e. nongenetic, drivers of health and disease. The external exposome comprises aspects of the built environment, the social environment, the physico-chemical environment and the lifestyle/food environment. The internal exposome comprises measurements at the epigenetic, transcript, proteome, microbiome or metabolome level to study either the exposures directly, the imprints these exposures leave in the biological system, the potential of the body to combat environmental insults and/or the biology itself. In this review, we describe the evidence for environmental risk factors of type 2 diabetes, focusing on both the general external exposome and imprints of this on the internal exposome. Studies provided established associations of air pollution, residential noise and area-level socioeconomic deprivation with an increased risk of type 2 diabetes, while neighbourhood walkability and green space are consistently associated with a reduced risk of type 2 diabetes. There is little or inconsistent evidence on the contribution of the food environment, other aspects of the social environment and outdoor temperature. These environmental factors are thought to affect type 2 diabetes risk mainly through mechanisms incorporating lifestyle factors such as physical activity or diet, the microbiome, inflammation or chronic stress. To further assess causality of these associations, future studies should focus on investigating the longitudinal effects of our environment (and changes to it) in relation to type 2 diabetes risk and whether these associations are explained by these proposed mechanisms. Graphical abstract: [Figure not available: see fulltext.

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our “modern” postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases.</p

Rehabilitation following first-time lumbar disc surgery: A systematic review within the framework of the Cochrane collaboration

Study Design. A systematic review of randomized controlled trials. Background. Although several rehabilitation programs, physical fitness programs, or protocols regarding instruction for patients to return to work after lumbar disc surgery have been suggested, little is known about the efficacy of these treatments, and there are still persistent fears of causing reinjury, reherniation, or instability. Objectives. The objective of this systematic review was to evaluate the effectiveness of active treatments that are used in the rehabilitation after first-time lumbar disc surgery. Methods. The authors searched the MEDLINE, Embase, and Psyclit databases up to April 2000 and the Cochrane Controlled Trials Register 2001, issue 3. Both randomized and nonrandomized controlled trials on any type of active rehabilitation program after first-time disc surgery were included. Two independent reviewers performed the inclusion of studies, and two other reviewers independently performed the methodologic quality assessment. A rating system that consists of four levels of scientific evidence summarizes the results. Results. Thirteen studies were included, six of which were of high quality. There is no strong evidence for the effectiveness for any treatment starting immediately post-surgery, mainly because of the lack of good quality studies. For treatments that start 4 to 6 weeks postsurgery, there is strong evidence (level 1) that intensive exercise programs are more effective on functional status and faster return to work (short-term follow-up) as compared to mild exercise programs, and there is strong evidence (level 1) that on long-term follow-up there is no difference between intensive exercise programs and mild exercise programs with regard to overall improvement. For all other primary outcome measures for the comparison between intensive and mild exercise programs, there is conflicting evidence (level 3) with regard to long-term follow-up. Furthermore, there is no strong evidence for the effectiveness of supervised training as compared to home exercises. There is also no strong evidence for the effectiveness of multidisciplinary rehabilitation as compared to usual care. There is limited evidence (level 3) that treatments in working populations that aim at return to work are more effective than usual care with regard to return to work. Also, there is limited evidence (level 3) that low-tech and high-tech exercises, started more than 12 months postsurgery, are more effective in improving low-back functional status as compared to physical agents, joint manipulations, or no treatment. Finally, there is no strong evidence for the effectiveness of any specific intervention when added to an exercise program, regardless of whether exercise programs start immediately postsurgery or later. None of the investigated treatments seem harmful with regard to reherniation or reoperation. Conclusions. There is no evidence that patients need to have their activities restricted after first-time lumbar disc surgery. There is strong evidence for intensive exercise programs (at least if started about 4-6 weeks post-operative) and no evidence they increase the reoperation rate. It is unclear what the exact content of postsurgery rehabilitation should be. Moreover, there are no studies that investigated whether active rehabilitation programs should start immediately postsurgery or possibly 4 to 6 weeks later

Behavioral graded activity following first-time lumbar disc surgery: 1-Year results of a randomized clinical trial

Study Design and Objectives. In a randomized clinical trial, the effectiveness of behavioral graded activity was assessed as compared to usual care provided by physiotherapists for patients after first-time lumbar disc surgery (n = 105). Summary of Background Data. Little is known about the effectiveness of rehabilitation programs following lumbar disc surgery. Most programs focus on biomechanical aspects, whereas psychosocial factors are hardly addressed. The aim of the behavioral graded activity program, which is an operant treatment, is to alter psychosocial factors such as fear of movement and pain catastrophizing, which might subsequently lead to improved functional status and higher rates of recovery. Behavioral treatments for patients following lumbar disc surgery have not yet been assessed in a randomized clinical trial. Methods. Inclusion criteria: age between 18 and 65 years; first-time lumbar disc surgery; restrictions in normal activities of daily living. Exclusion criteria: surgical complications and confirmed and relevant underlying diseases. Outcome assessment took place at 6 and 12 months after randomization. Results. Six months after randomization, 62% of the patients had recovered following usual care versus 65% of the patients following behavioral graded activity. After 12 months, 73% and 75%, respectively, had recovered. Differences between intervention groups, 3% and 2% respectively, after 6 and 12 months are not statistically significant. Furthermore, there were no differences between the two groups regarding functional status, pain, pain catastrophizing, fear of movement, range of motion, general health, social functioning or return to work. After 1 year, 4 of the behavioral graded activity cases had undergone another operation versus 2 of usual care cases. Conclusion. Both fear of movement and pain catastrophizing seem to be unaffected by either treatment in these patients. It is concluded that treatment principles derived from theories within the field of chronic low back pain might not apply to these patients. After 1 year of follow-up, there were no statistically significant or clinically relevant differences between the behavioral graded activity program and usual care as provided by physiotherapists for patients following first-time lumbar disc surgery

Behavioral-graded activity compared with usual care after first-time disk surgery: Considerations of the design of a randomized clinical trial

Objective: To present the design of a trial on the effectiveness of a behavioral-graded activity model. Design: Randomized clinical trial. Patients: Patients undergoing first-time lumbar disk surgery who still have low-back pain at the 6-week neurosurgical consultation. Interventions: A patient-tailored behavioral graded activity program that is based on operant therapy. The key elements of this program are baseline measurements, goal-setting, and time-contingency. This program is compared with usual care in physiotherapy, which is pain-contingent. Outcome Measures: Primary measures are the patient's global impression of the effect and their functional status. Secondary measures are kinesiophobia, catastrophizing, pain, main complaint, range of motion, and relapses. The direct and indirect costs will also be assessed. The effect measures are rated before randomization and 3, 6, and 12 months later. Discussion: Several trials have been conducted on the effectiveness of behavioral treatments. Subjects were always patients with chronic low-back pain. In this trial, we apply such a treatment in patients after first-time disk surgery in a primary care setting

Environmental risk factors of type 2 diabetes-an exposome approach

Type 2 diabetes is one of the major chronic diseases accounting for a substantial proportion of disease burden in Western countries. The majority of the burden of type 2 diabetes is attributed to environmental risks and modifiable risk factors such as lifestyle. The environment we live in, and changes to it, can thus contribute substantially to the prevention of type 2 diabetes at a population level. The ‘exposome’ represents the (measurable) totality of environmental, i.e. nongenetic, drivers of health and disease. The external exposome comprises aspects of the built environment, the social environment, the physico-chemical environment and the lifestyle/food environment. The internal exposome comprises measurements at the epigenetic, transcript, proteome, microbiome or metabolome level to study either the exposures directly, the imprints these exposures leave in the biological system, the potential of the body to combat environmental insults and/or the biology itself. In this review, we describe the evidence for environmental risk factors of type 2 diabetes, focusing on both the general external exposome and imprints of this on the internal exposome. Studies provided established associations of air pollution, residential noise and area-level socioeconomic deprivation with an increased risk of type 2 diabetes, while neighbourhood walkability and green space are consistently associated with a reduced risk of type 2 diabetes. There is little or inconsistent evidence on the contribution of the food environment, other aspects of the social environment and outdoor temperature. These environmental factors are thought to affect type 2 diabetes risk mainly through mechanisms incorporating lifestyle factors such as physical activity or diet, the microbiome, inflammation or chronic stress. To further assess causality of these associations, future studies should focus on investigating the longitudinal effects of our environment (and changes to it) in relation to type 2 diabetes risk and whether these associations are explained by these proposed mechanisms

A two dimensional electromechanical model of a cardiomyocyte to assess intra-cellular regional mechanical heterogeneities

Experimental studies on isolated cardiomyocytes from different animal species and human hearts have demonstrated that there are regional differences in the Ca2+ release, Ca2+ decay and sarcomere deformation. Local deformation heterogeneities can occur due to a combination of factors: regional/local differences in Ca2+ release and/or re-uptake, intra-cellular material properties, sarcomere proteins and distribution of the intracellular organelles. To investigate the possible causes of these heterogeneities, we developed a two-dimensional finite-element electromechanical model of a cardiomyocyte that takes into account the experimentally measured local deformation and cytosolic [Ca2+] to locally define the different variables of the constitutive equations describing the electro/mechanical behaviour of the cell. Then, the model was individualised to three different rat cardiac cells. The local [Ca2+] transients were used to define the [Ca2+]-dependent activation functions. The cell-specific local Young’s moduli were estimated by solving an inverse problem, minimizing the error between the measured and simulated local deformations along the longitudinal axis of the cell. We found that heterogeneities in the deformation during contraction were determined mainly by the local elasticity rather than the local amount of Ca2+, while in the relaxation phase deformation was mainly influenced by Ca2+ re-uptake. Our electromechanical model was able to successfully estimate the local elasticity along the longitudinal direction in three different cells. In conclusion, our proposed model seems to be a good approximation to assess the heterogeneous intracellular mechanical properties to help in the understanding of the underlying mechanisms of cardiomyocyte dysfunction.This study was partly supported by grants from Ministerio de Economia y Competitividad (ref. SAF2012-37196, TIN2014-52923-R); the Instituto de Salud Carlos III (ref. PI11/01709, PI14/00226) integrado en el Plan Nacional de I+D+I y cofinanciado por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) “Otra manera de hacer Europa”; the EU FP7 for research, technological development and demonstration under grant agreement VP2HF (n° 611823); The Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); Obra Social “la Caixa” (Barcelona, Spain); Fundació Mutua Madrileña; Fundació Agrupació Mutua (Spain) and AGAUR 2014 SGR grant n° 928 (Barcelona, Spain). P.G.C. was supported by the Programa de Ayudas Predoctorales de Formación en investigación en Salud (FI12/00362) from the Instituto Carlos III, Spain. P.G.C wants to acknowledge to Boehringer Ingelhiem Fonds for the travel grant to do her research stay at LaBS group in Politecnico di Milano

LongITools:dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

Abstract The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our ”modern” postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases